Efficacy of a Synthetic Vaccine Derived From Plasmodium Vivax Circumsporozoite Protein (PvCS) in naïve and Semi-immune Volunteers

Summary

This is a randomized, double-blind, controlled, which seeks to compare two groups of volunteers (naive and previously exposed to malaria) vaccinated with three doses of a synthetic derivative of the CS protein of Plasmodium vivax to determine their protective efficacy. Then volunteers will be subject to an infectious challenge (Controlled Human Malaria Infection) to assess the infectivity of gametocytes in the blood early stage of P. vivax in Anopheles albimanus mosquitoes.

Timeline

Start

2021-06-01

Primary completion

2022-06-01

Completion

2022-12-01

Publications

• Background Ademolue TW, Awandare GA. Evaluating antidisease immunity to malaria and implications for vaccine design. Immunology. 2018 Apr;153(4):423-434. doi: 10.1111/imm.12877. Epub 2017 Dec 26.
• Background RTS,S Clinical Trials Partnership. Efficacy and safety of the RTS,S/AS01 malaria vaccine during 18 months after vaccination: a phase 3 randomized, controlled trial in children and young infants at 11 African sites. PLoS Med. 2014 Jul 29;11(7):e1001685. doi: 10.1371/journal.pmed.1001685. eCollection 2014 Jul.
• Background Aliprandini E, Tavares J, Panatieri RH, Thiberge S, Yamamoto MM, Silvie O, Ishino T, Yuda M, Dartevelle S, Traincard F, Boscardin SB, Amino R. Cytotoxic anti-circumsporozoite antibodies target malaria sporozoites in the host skin. Nat Microbiol. 2018 Nov;3(11):1224-1233. doi: 10.1038/s41564-018-0254-z. Epub 2018 Oct 22.
• Background Arevalo-Herrera M, Herrera S. Plasmodium vivax malaria vaccine development. Mol Immunol. 2001 Dec;38(6):443-55. doi: 10.1016/s0161-5890(01)00080-3.
• Background Arevalo-Herrera M, Roggero MA, Gonzalez JM, Vergara J, Corradin G, Lopez JA, Herrera S. Mapping and comparison of the B-cell epitopes recognized on the Plasmodium vivax circumsporozoite protein by immune Colombians and immunized Aotus monkeys. Ann Trop Med Parasitol. 1998 Jul;92(5):539-51.
• Background Arevalo-Herrera M, Soto L, Perlaza BL, Cespedes N, Vera O, Lenis AM, Bonelo A, Corradin G, Herrera S. Antibody-mediated and cellular immune responses induced in naive volunteers by vaccination with long synthetic peptides derived from the Plasmodium vivax circumsporozoite protein. Am J Trop Med Hyg. 2011 Feb;84(2 Suppl):35-42. doi: 10.4269/ajtmh.2011.09-0507.
• Background Arevalo-Herrera M, Chitnis C, Herrera S. Current status of Plasmodium vivax vaccine. Hum Vaccin. 2010 Jan;6(1):124-32. doi: 10.4161/hv.6.1.9931. Epub 2010 Jan 26.
• Background Arnot DE, Stewart MJ, Barnwell JW. Antigenic diversity in Thai Plasmodium vivax circumsporozoite proteins. Mol Biochem Parasitol. 1990 Nov;43(1):147-9. doi: 10.1016/0166-6851(90)90140-h. No abstract available.
• Background Arnot DE, Barnwell JW, Tam JP, Nussenzweig V, Nussenzweig RS, Enea V. Circumsporozoite protein of Plasmodium vivax: gene cloning and characterization of the immunodominant epitope. Science. 1985 Nov 15;230(4727):815-8. doi: 10.1126/science.2414847.
• Background Barnwell JW, Galinski MR. Plasmodium vivax: a glimpse into the unique and shared biology of the merozoite. Ann Trop Med Parasitol. 1995 Apr;89(2):113-20. doi: 10.1080/00034983.1995.11812941.
• Background Barnwell JW, Galinski MR, DeSimone SG, Perler F, Ingravallo P. Plasmodium vivax, P. cynomolgi, and P. knowlesi: identification of homologue proteins associated with the surface of merozoites. Exp Parasitol. 1999 Mar;91(3):238-49. doi: 10.1006/expr.1998.4372.
• Background Bermudez M, Moreno-Perez DA, Arevalo-Pinzon G, Curtidor H, Patarroyo MA. Plasmodium vivax in vitro continuous culture: the spoke in the wheel. Malar J. 2018 Aug 20;17(1):301. doi: 10.1186/s12936-018-2456-5.
• Background Burkot TR, Wirtz RA, Paru R, Garner P, Alpers MP. The population dynamics in mosquitoes and humans of two Plasmodium vivax polymorphs distinguished by different circumsporozoite protein repeat regions. Am J Trop Med Hyg. 1992 Dec;47(6):778-86. doi: 10.4269/ajtmh.1992.47.778.
• Background Cattani JA, Tulloch JL, Vrbova H, Jolley D, Gibson FD, Moir JS, Heywood PF, Alpers MP, Stevenson A, Clancy R. The epidemiology of malaria in a population surrounding Madang, Papua New Guinea. Am J Trop Med Hyg. 1986 Jan;35(1):3-15. doi: 10.4269/ajtmh.1986.35.3.
• Background Cerami C, Frevert U, Sinnis P, Takacs B, Clavijo P, Santos MJ, Nussenzweig V. The basolateral domain of the hepatocyte plasma membrane bears receptors for the circumsporozoite protein of Plasmodium falciparum sporozoites. Cell. 1992 Sep 18;70(6):1021-33. doi: 10.1016/0092-8674(92)90251-7.
• Background CDC (2020) 'CDC - Malaria - Malaria Worldwide - Impact of Malaria'. Available in: https://www.cdc.gov/malaria/malaria_worldwide/impact.html
• Background Clyde DF. Immunization of man against falciparum and vivax malaria by use of attenuated sporozoites. Am J Trop Med Hyg. 1975 May;24(3):397-401. doi: 10.4269/ajtmh.1975.24.397.
• Background Clyde DF, McCarthy VC, Miller RM, Hornick RB. Specificity of protection of man immunized against sporozoite-induced falciparum malaria. Am J Med Sci. 1973 Dec;266(6):398-403. doi: 10.1097/00000441-197312000-00001. No abstract available.
• Background Cochrane AH, Aikawa M, Jeng M, Nussenzweig RS. Antibody-induced ultrastructural changes of malarial sporozoites. J Immunol. 1976 Mar;116(3):859-67.
• Background Cochrane AH, Nardin EH, de Arruda M, Maracic M, Clavijo P, Collins WE, Nussenzweig RS. Widespread reactivity of human sera with a variant repeat of the circumsporozoite protein of Plasmodium vivax. Am J Trop Med Hyg. 1990 Nov;43(5):446-51. doi: 10.4269/ajtmh.1990.43.446.
• Background Collins WE, Jeffery GM. A retrospective examination of sporozoite- and trophozoite-induced infections with Plasmodium falciparum in patients previously infected with heterologous species of Plasmodium: effect on development of parasitologic and clinical immunity. Am J Trop Med Hyg. 1999 Jul;61(1 Suppl):36-43. doi: 10.4269/tropmed.1999.61-036.
• Background Collins WE, Sullivan JS, Morris CL, Galland GG, Richardson BB. Observations on the biological nature of Plasmodium vivax sporozoites. J Parasitol. 1996 Apr;82(2):216-9.
• Background Comer RD, Young MD, Porter JA Jr, Gauld JR, Merritt W. Chloroquine resistance in Plasmodium falciparum malaria on the Pacific coast of Colombia. Am J Trop Med Hyg. 1968 Nov;17(6):795-9. doi: 10.4269/ajtmh.1968.17.795. No abstract available.
• Background Charoenvit Y, Collins WE, Jones TR, Millet P, Yuan L, Campbell GH, Beaudoin RL, Broderson JR, Hoffman SL. Inability of malaria vaccine to induce antibodies to a protective epitope within its sequence. Science. 1991 Feb 8;251(4994):668-71. doi: 10.1126/science.1704150.
• Background Chitnis CE. Molecular insights into receptors used by malaria parasites for erythrocyte invasion. Curr Opin Hematol. 2001 Mar;8(2):85-91. doi: 10.1097/00062752-200103000-00005.
• Results Arevalo-Herrera M, Vera O, Castellanos A, Cespedes N, Soto L, Corradin G, Herrera S. Preclinical vaccine study of Plasmodium vivax circumsporozoite protein derived-synthetic polypeptides formulated in montanide ISA 720 and montanide ISA 51 adjuvants. Am J Trop Med Hyg. 2011 Feb;84(2 Suppl):21-7. doi: 10.4269/ajtmh.2011.10-0110.

Drugs

Indications